B6;129-Bub1b^{Gt(neo-btk)1Dai}/J

Stock number: 010495
Research areas: Cancer Research, Developmental Biology Research, Hematological Research

Description

Mice heterozygous for this mutation in the budding uninhibited by benzimidazoles 1 homolog (Bub1b) gene exhibit splenomegaly, an increase in extramedullary megakaryocytes and reduced numbers of peripheral red blood cells. This mutant mouse strain may be useful in studies of early embryonic development, hematopoiesis, megakaryopoiesis, tumorigenesis and genomic instability.

Detailed description

Mice heterozygous for this mutation exhibit splenomegaly accompanied by a loss of marginal zone boundaries and an increase in mature megakaryocytes. Approximately 50% of mice have significantly reduced numbers of peripheral red blood cells, however platelet numbers are not increased. Homozygous embryos do not survive beyond early gestation (E8.5) due to impaired blastocyst proliferation and extensive apoptosis. Mouse embryonic fibroblasts from heterozygous mice exhibit defective spindle checkpoint activation, an important mechanism for genomic stability. In addition, mice are susceptible to development of lung and colon adenocarcinomas following challenge with carcinogen. Mice homozygous for the mutation are embryonic lethal. This mutant mouse strain may be useful in studies of early embryonic development, hematopoiesis, megakaryopoiesis tumorigenesis and genomic instability.

Development

A retroviral genetrap vector with a splice acceptor fused to neo with a poly A signal and a PGK promoter fused to the coding sequence of the BTK gene with a splice donor site was used to disrupt intron 1 between exon 1 and 2 of the endogenous gene. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Heterozygous offspring were crossed to C57BL/6 and then maintained by intercross.

Allele

Symbol: Bub1b^{Gt(neo-btk)1Dai}
Name: gene trap 1, Wei Dai
MGI accession ID: MGI:3033386
Generation method: Gene trapped
Attributes: Reporter; Null/Knockout
Marker symbol: Bub1b
Marker name: BUB1B, mitotic checkpoint serine/threonine kinase
Chromosome: 2
Strain of origin: 129S4/SvJae
Molecular note: The endogenous gene was disrupted by the integration of a gene trap vector into intron 1. The gene trap vector contained a splice acceptor, neo, a polyadenylation signal, PGK-btk, and a a splice donor.